Continuous Flow Transetherification of Vinylogous Esters and Their Reverse Reaction Using Fe-Catalyst

Abstract

Vinylogous esters have been widely used as a key intermediate in synthetic organic chemistry. In particular, they have been used as synthons in natural products and drug synthesis. Many vinylogous esters have been found in the core structure of several compounds having a wide range of biological activity. Furthermore, this type of compounds were also used as a source of dienophiles in Diels-Alder reactions and precursor for many terpenoid syntheses. However, this compound prone to undergoes reversible reaction under acidic environment results in no reaction or poor yields. Therefore, special attention has been considered for their synthesis. Several reported batch conditions poses a serious concern on reversibility, yield and scalability. Therefore novel process which can overcome the batch condition is highly desirable. In this dissertation, we have studied the continuous flow approach for the synthesis of vinylogous esters using environmentally benign, less toxic, cheap, and commercially available Fe-catalyst. Moreover, this approach is highly efficient, operationally simple, additive free and chemoselective for transetherification of vinylogous esters from different alcohols. We have also studied for the scalability and sequential transetherification using Fe homogeneous and heterogeneous catalyst. Besides, the deprotection of vinylogous esters in water using a catalytic amount of FeCl3·6H2O (5 mol%) have also been achieved. The synthetic applications of vinylogous esters also shown by coupling reactions, spiro compound synthesis and aromatisation reactions.